Targeted Natural Interventions

Magnesium. Magnesium is required to maintain smooth muscle relaxation in blood vessels (D’Angelo 1992). The requirement for magnesium increases with physical and emotional stress, both of which are known to trigger episodes of Raynaud’s phenomenon, and there is some evidence that levels of magnesium in the red blood cells from women with Raynaud’s phenomenon drop in the winter compared to healthy controls (Seelig 1994; Herrick 2012; Leppert 1994a). Low magnesium levels can increase smooth muscle contractility in blood vessels, which is important because blood vessel constriction is an important aspect of Raynaud’s phenomenon (Leppert 1994b). One study found that decreased serum magnesium levels were more common in women who experience Raynaud’s phenomenon when exposed to cold than in healthy women (82% and 45%, respectively) (Leppert 1990). Studies evaluating magnesium infusion in women with primary Raynaud’s phenomenon found that it helped normalize levels of magnesium as well as levels of certain hormones, proteins, and enzymes associated with the condition (Myrdal 1994; Leppert 1994a,b; Leppert 1995).

N-Acetylcysteine (NAC). This powerful antioxidant supports the production of glutathione, which in turn helps prevent damage to the blood vessel lining. A small study in 22 patients with Raynaud’s phenomenon secondary to systemic sclerosis found that those receiving a continuous, 5-day intravenous infusion of NAC had fewer and less-severe attacks (Sambo 2001). In another study, for two years, patients received 15 mg/kg per hour intravenous NAC infusions for 5 consecutive hours every 2 weeks. Researchers found that this treatment enhanced blood flow in the hands, reduced the severity and frequency of Raynaud’s phenomenon attacks, and increased vasodilation (Salsano 2005). Another study, in which 50 patients with systemic sclerosis received NAC infusions every 2 weeks for a median duration of 3 years, reported that the therapy was beneficial for Raynaud’s phenomenon and finger ulcers related to insufficient blood flow; reductions in frequency of attacks, finger ulcers, and pain were observed (Rosato 2009).

Yohimbine. Yohimbine, derived from the bark of the yohimbie tree, is a chemical that blocks alpha-2 receptors, which are involved in vasoconstriction. The use of this compound in Raynaud’s phenomenon stems from the observation that patients with primary Raynaud’s phenomenon show abnormal alpha-adrenergic responses. In a laboratory study on blood vessels from 50 subjects who underwent hand surgery for reasons not related to vascular disease, it was noted that yohimbine reversed cold-induced blood vessel contraction (Bodelsson 1990). Another study enrolled 23 patients, and after cold-induced primary Raynaud’s phenomenon was triggered, participants were randomly assigned to receive one of the following three treatments: an intra-arterial infusion of yohimbine, the alpha-1 receptor blocker prazosin, or the 2 treatments combined. The authors reported that fewer fingers, overall, developed attacks in the yohimbine group and combined treatment group than in the prazosin group (Freedman 1995). It should be noted that yohimbine may cause a fast heartbeat or elevated blood pressure in some individuals.

Vitamin C. Vitamin C, also known as ascorbic acid, is important for the synthesis of collagen, a key component of blood vessel walls (Nusgens 2001). In addition, studies suggest vitamin C supplementation improves blood flow (Kirby 2009). There is also evidence that people with Raynaud’s phenomenon have low levels of ascorbic acid. In one study, researchers found that median plasma levels of vitamin C were 4.8 mg/L in patients with primary Raynaud’s phenomenon, 2.5 mg/L in those with limited cutaneous systemic sclerosis, and 6.8 mg/L in those with diffuse systemic sclerosis; all values were significantly lower than 10.6 mg/L, which was observed in healthy control subjects (Herrick 1994). Another study found that 500 mg per day of vitamin C for 30 days promoted vasodilation and improved blood flow in people with coronary artery atherosclerosis, a condition that shares some risk factors with secondary Raynaud’s phenomenon (Gokce 1999; NCBI 2011).

Essential fatty acids. Omega-3 fatty acids such as eicosapentaenoic acid (EPA) and decosahexaenoic aicd (DHA) found in fish oil, and gamma-linolenic acid (GLA), a healthy omega-6 fatty acid found in evening primrose oil and borage oil, have blood-thinning effects that may help relieve symptoms of Raynaud’s phenomenon. One study found that 12 capsules per day for 8 weeks of evening primrose oil significantly reduced the number and severity of primary Raynaud’s phenomenon attacks (Belch 1985). Another study on fish oil supplementation found that 12 fish-oil capsules daily containing a total of 3.96 g EPA and 2.64 g DHA taken for 12 weeks increased the time before symptoms appeared after cold exposure compared to placebo in primary Raynaud’s phenomenon. This treatment also significantly increased blood flow in the fingers in participants with primary Raynaud’s phenomenon, as compared to a control group that received olive-oil capsules (DiGiacomo 1989).

L-Arginine. The amino acid L-arginine is important for the synthesis of nitric oxide, a potent vasodilator (Rembold 2003; Cooke 2005). In 2003, a case report described 2 patients with severe Raynaud’s phenomenon in whom oral L-arginine supplementation reversed necrosis of tissue in the fingers or toes (Rembold 2003). In another study that included individuals with Raynaud’s phenomenon secondary to systemic sclerosis, the authors reported that warming patients’ fingers after L-arginine treatment led to an increase in blood flow. In addition, another study showed that L-arginine (administered orally; 4 g twice daily) modulated blood vessel response to cool temperatures in the fingers of individuals with systemic sclerosis (Agostoni 1991).

Vitamin D. A study on 42 people with low vitamin D blood levels (average 20.9 ng/mL) and Raynaud’s phenomenon reported that subjects receiving 600 000 IU of oral vitamin D3 per month for 2 months not only achieved higher blood levels of vitamin D than those receiving placebo (32.9 ng/mL versus 23.2 ng/mL), but also reported their Raynaud’s became less severe. Researchers speculated that vitamin D may function as a vasodilator in individuals with Raynaud’s phenomenon (Helou 2012). Although more studies need to evaluate the role of vitamin D in Raynaud’s phenomenon, individuals with this condition are encouraged to have a blood test to assess their levels of 25-hydroxyvitamin D, and use a daily vitamin D3 supplement to maintain their levels between 50 and 80 ng/mL.

Vitamin E. Vitamin E is an antioxidant that protects fatty acids and other cellular molecules from oxidative damage (Brigelius-Flohe 1999). Some reports indicate that low levels of vitamin E are associated with Raynaud’s phenomenon (Simonini 2000). One study on individuals experiencing Raynaud’s as a consequence of working with vibrating machinery found that supplementation with 600 mg of alpha-tocopherol nicotinate daily for 6 weeks improved subjective symptoms such as numbness and cold sensation; clinical examinations also indicated improvement (Matoba 1977).

Gingko biloba. A study exploring the effectiveness of 120 mg Gingko biloba extract taken 3 times per day (for a total of 360 mg/day) for 10 weeks found that treatment reduced the number of Raynaud’s phenomenon attacks per week by 56%, compared to 27% in the placebo group (Muir 2002). In addition, a study on mice found that intravenous administration of a Gingko biloba extract inhibited vasoconstriction induced by platelet activation, suggesting ginkgo may also attenuate the vasoconstriction that occurs during an attack of Raynaud’s phenomenon (Stücker 1997).

Niacin and inositol hexanicotinate. Niacin, or vitamin B3, improves peripheral vasodilation, helps prevent formation of blood clots, and modulates lipid metabolism (Rosenson 2003; Kamanna 2009). Inositol hexanicotinate is a compound containing inositol bound to six molecules of niacin; within the body, niacin is released from the inositol (Milton 2013). An 84-day study evaluated the effectiveness of 4 g/day inositol hexanicotinate in 23 patients with primary Raynaud’s phenomenon. The inositol hexanicotinate group reported feeling better, and their attacks were shorter and fewer compared to placebo (Sunderland 1988). Another study using inositol hexanicotinate in 30 patients with primary or secondary Raynaud’s phenomenon reported that severity of vasoconstriction attacks decreased in most participants; non-smokers responded faster to therapy than smokers. In addition, elderly participants with longstanding vasospastic disease showed improved blood flow as a result of treatment. No side effects were reported (Holti 1979).

Selenium. The mineral selenium is an important component of several enzymes involved in intrinsic antioxidant defense mechanisms within the body; low selenium levels can compromise the body’s ability to combat free radical damage (Tikly 2006). Studies report low levels of selenium in people with Raynaud’s phenomenon and particularly those with systemic sclerosis, suggesting that supplementation may be of benefit in this population (Herrick 1994). These findings are particularly important in the context of Raynaud’s phenomenon secondary to systemic sclerosis, since oxidative stress is a significant contributor to the endothelial dysfunction that underlies this condition (Simonini 2000).

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